血小板的促轉(zhuǎn)移的作用早已確認(rèn)，血小板對和腫瘤轉(zhuǎn)移的貢獻(xiàn)包括屏蔽NK細(xì)胞對腫瘤細(xì)胞的殺傷作用,，協(xié)助腫瘤細(xì)胞與內(nèi)皮細(xì)胞之間的粘附,，血小板P-選擇素促進(jìn)腫瘤細(xì)胞的出血管。
然而,，血小板促轉(zhuǎn)移功能的許多方面仍不清楚,。在一項(xiàng)最新研究中，科研人員用轉(zhuǎn)移性乳腺癌和黑色素瘤小鼠模型以探討血小板的作用,，研究主要側(cè)重于腫瘤轉(zhuǎn)移的器官特異性問題,，重點(diǎn)考察腫瘤轉(zhuǎn)移是否與NK細(xì)胞和血小板衍生與內(nèi)皮細(xì)胞來源的P-選擇素相關(guān)。
在實(shí)驗(yàn)性和自發(fā)轉(zhuǎn)移模型中,，我們發(fā)現(xiàn)在NK細(xì)胞不存在的情況下,，血小板會促進(jìn)腫瘤的肺轉(zhuǎn)移。此外,，血小板的促腫瘤轉(zhuǎn)移具有器官特異性,，雖然明確提高肺轉(zhuǎn)移，但并不影響B(tài)16F1的肝轉(zhuǎn)移,，事實(shí)上,，肝轉(zhuǎn)移發(fā)生在血小板缺失的情況下。此外,，血小板的存在與否不影響NK細(xì)胞抗轉(zhuǎn)移的活性,，血小板的促轉(zhuǎn)移的作用具有時(shí)間上的差異性,。
最后，研究表明內(nèi)皮細(xì)胞源性P-選擇素與血小板衍生的P-選擇素一樣是重要的促進(jìn)肺轉(zhuǎn)移,、肝轉(zhuǎn)移的生物活性因子。該項(xiàng)研究結(jié)果有助于闡明血小板,、NK細(xì)胞和P-選擇素對腫瘤轉(zhuǎn)移的作用,，并提示P-選擇素是一個(gè)有前景的防止腫瘤多器官轉(zhuǎn)移的治療靶標(biāo)。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-4010
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Platelets and P-selectin control tumor cell metastasis in an organ-specific manner and independently of NK cells
Lucy A. Coupland1, Beng H. Chong2, and Christopher R. Parish3,*
The pro-metastatic role of platelets has long been recognized with proposed mechanisms of action including shielding tumor cells from NK cell destruction and aiding endothelial attachment and extravasation of tumor cells with platelet P-selectin being implicated in these processes. However, many aspects of the pro-metastatic function of platelets remain unclear. In this study, we used mouse models of metastatic breast cancer and melanoma to investigate the platelet effect, focusing on organ specificity, the relationship with NK cells and the relative importance of platelet-derived versus endothelial-derived P-selectin. We found that platelets promote lung metastasis in the absence of NK cells in both acute and spontaneous metastasis models. Additionally, the pro-metastatic action of platelets was found to be organ specific, clearly enhancing lung metastasis but not affecting B16F1 liver metastasis, in fact, liver metastasis was enhanced in the absence of platelets. Furthermore, the profound anti-metastatic activity of NK cells was equally effective in the presence or absence of platelets and chronologically distinct from the pro-metastatic role of platelets. Lastly, it was shown that endothelial-derived P-selectin is just as important as platelet-derived P-selectin in promoting lung metastasis and also plays an important role in liver metastasis. Taken together, our findings help clarify the roles of platelets, NK cells and P-selectin in metastasis, and they identify P-selectin as an attractive therapeutic target for preventing metastasis in multiple organs.
